PARENTERAL ROUTE OF DRUG ADMINISTRATION The term parenteral refers to injectable routes of administration of drug. So as a hole it means outside of intestine. PARENTRAL MEDICATIONS AND STERILE FLUIDS: The parenteral route of drug administration are: 1. Intravenous IV 2. Intramuscular IM 3. Intradermal 4. Subcutaneous PYROGENS: The water used in parenteral should be free of pyrogens. METHODS OF REMOVING PYROGENS: 1. Distillation 2. Reverse osmosis 3. Heating at 180 degree celcius for 3 to 4 hours 4. Adsorption method OFFICIAL TYPES OF INJECTIONS: SOLVENTS AND VEHICLES USED FOR INJECTIONS: STERILE WATER FOR INJECTION USP BACTERIOSTATIC WATER FOR INJECTION NaCl injection USP BACTERIOSTATIC SODIUM CHLORIDE INJECTION USP RINGER INJECTION USP LACTATED RINGER INJECTION USP NON AQUEOUS VEHICLES ADDED SUBSTANCES USED IN PARENTERALS SOLUBILIZING AGENTS STABILIZERS ANTIMICROBIAL AGENTS ANTI OXIDANTS USED IN PARENTERALS.

3. PARENTERAL ROUTE OF
DRUG ADMINISTRATION

4. PARENTERAL MEDICATIONS
AND STERILE FLUIDS
• The term parental refers to the injectable route of
administration.
• The word parental have been derived from the two Greek
words, “ para “ means ‘ outside or away from ‘ and the word “
enteron “ means ‘intestine’.
• So as a whole it means outside of the intestine.

5. PARENTAL ROUTES FOR
ADMINISTRATION
• The parental routes for administration are;
1. Intravenous IV
2. Intramuscular IM
3. Intra dermal
4. Subcutaneous

7. INJECTIONS
What are injection?
• Injections are sterile, micro organism and pyrogen
free preparations intended to be administered from
parental routes.

9. PYROGENS
What are Pyrogens?
• The water used in the parental and irrigating solutions should
be free of pyrogens.
• They are the products of the metabolism of organism.
• Most bacteria and many molds , viruses produce the pyrogen.
• The gram negative bacteria produce the most pyrogenic
substances.
• Chemically they are lipid substances associated with
carrier molecules which are usually a polysaccharides or a
protein.
• Pyrogen produce rise in body temperature , chills , body
ache , vasoconstriction and rise in blood pressure.

10. METHODS OF REMOVING
PYROGENS
• Following are the methods of removing
pyrogens;
1. Distillation
2. Reverse osmosis
3. Heating at 180 degree Celsius for 3 to 4 hours
4. Adsorption method

11. OFFICIAL TYPES OF
INJECTIONS
• According to the USP , injections are separated into
five distinct types;
1. The medicaments or solutions or emulsions suitable
for injection ( e.g. Insulin injection USP )
2. Dry solids or liquid concentrates containing no
buffers , diluents , or other added substances and
which upon the addition of suitable solvents yield
solution. Confirming it all aspects to requirements for
injections ( e.g. sterile ampicillin sodium USP )

12. 3. Dry solids or liquid concentrates containing buffers ,
diluents or other added substances (e.g. methicillin
sodium for injection USO).
4. Solid which are suspended in a suitable fluid medicine
and which are not to be injected intravenously or into
spinal canal ( e.g. sterile dexamethasone acetate
suspension USP ). It is given intra articular ( i.e. soft
tissues and joints ).
5. Dry solid which upon the addition of suitable vehicles
yield the preparations the requirements for sterile
suspensions ( e.g. sterile ampicillin for suspension
USP ).

13. SOLVENTS AND VEHICLES
USED FOR INJECTIONS
• Most frequent used solvents in large scale manufacturing
of injection is “water for injection USP” this water is
purified by distillation or by reverse osmosis and
containing total solids not more than 1mg/100ml.
• This water for injection may not contain added substances
and it must be pyrogen free.
• Water which is intended to be used in the manufacturing
of injectable products must be sterilized after their
preparations.
• T6 is stored in tight containers at the temperature below
or above the range in which microbial growth occurs.

14. STERILE WATER FOR
INJECTION USP
• It is water for injection which is sterilized and packaged in
single dose container of not more than one liter size as water
for injection.
• It is pyrogen free and may not contain antimicrobial agent or
other added substances.
• They are used for reconstitution of multiple antibiotics.
• In use water is aseptically added to vial of medication to
prepare desired injection.
EXAMPLE;
A suitable injection may be prepared from the dry
powder sterile ampicillin sodium USP by the aseptic
addition of sterile water for injection USP.

15. BACTERIOSTATIC WATER FOR
INJECTION
• It is sterile water for injection containing one or more suitable
antimicrobial agent.
• It is placed into prefilled syringes on in vials containing not
more than 30ml of the water.
• The container label must state the name and proportion of
antimicrobial agent.
• This water is employed as sterile vehicle in the preparation of
small volume of injectables.
• It is used in parentals.
• Administered in large volume is restricted due to excessive
and toxic amount of antimicrobial agents which would be
injected along with the medicament.

16. NaCl INJECTION USP
• It is a sterile isotonic solution of sodium chloride in water for
injection.
• This solution is may be used in preparation of solutions and
suspensions of drugs for parental administration.

17. BACTERIOSTATIC SODIUM
CHLORIDE INJECTION USP
• It contains one or more suitable anti microbial agents which
must be specified on the labeling.
• Sodium chloride is present at 0.9% concentration to render the
solution isotonic.
• USP labeling requirement demand that the label must state,
“not for use in newborns”.
• Due to toxicity of bacteriostatic agent for example benzyl
alcohol.
• This toxicity may result from high cumulative amounts
(mg/kg ) of benzyl alcohol and limited detoxification capacity
of neonate’s liver.
• This solution does not cause problem in child and adult.

18. RINGER INJECTION USP
• It is a sterile solution of sodium chloride ,
potassium chloride , and calcium chloride in
water.
• These three agents are present in concentrated
similar to that present in physiologic fluids.
• It is employed as a vehicles for other drugs or
alone as an electrolyte replenisher and fluids
extender.

19. LACTATED RINGER INJECTION
USP
• It has different quantities of the same
three salts in ringer injection and contains
sodium lactate.
• This injection is a fluid and electrolyte
replenisher , systemic alkalizer.

20. NON AQUEOUS VEHICLES
• Due to limited water solubility of medicinal substances or due
to hydrolysis pharmaceutical formulator must use non aqueous
vehicles.
PROPERTIES OF NON AQUEOUS VEHICLES;
1. Selected vehicle must be non irritating , non toxic
, and non sensitizing in the amount administer.
2. It must not exert its own pharmacological actions.
3. It must not affect the activity on medicinal
substances.

21. THE CONSIDERATION IN THE SELECTION
OF NON AQUEOUS VEHICLE
1. The solvents physical and chemical stability at various pH level.
2. It viscosity , which must be such as to allow ease of injection.
3. Its fluidity which must be maintained over a wide range of temperature.
4. Its boiling point must be sufficiently high to permit heat sterilization.
5. Non aqueous solvents include fixed vegetable oils e.g. glycerin , polyethylene
glycols , propylene glycol , alcohols and number of agents which are used
like ethyl acetate.
6. These are safe in the amount administer and don’t interfere with therapeutic
efficacy of preparations.
7. The oil must not contains mineral oils or paraffin because they are not
absorbed by blood tissues.
8. Most common used fixed oil in injections are corn oil , seed oil , peanut oil ,
castor oil , and olive oil.
9. Oleaginous injections are administered intra muscularly but not be given
intravenously because oil globules will occlude the pulmonary
microcirculation.

22. ADDED SUBSTANCES USED IN
THE PARENTERAL
Added substances includes :
1. Solubilizing agents
2. Antitoxidants
3. Chelating agents
4. Buffers
5. Tonicity builders
6. Antibacterial agents
7. Hydrolysis inhibitors
8. Antifoaming agents.

23. SOLUBILIZING AGENTS
• A large number of solubilizing agents ( wetting agents ,
suspending agents , emulsifiers etc ) are used in parenteral
products to enhance the solubility of the slightly soluble drugs
in parenteral preparation.
• A review of commercially available injectable solution
formulations reveals that the solubilizing excipients majorly
include;
• The chemical techniques to solubilize water- insoluble drugs
for injection administration include pH adjustment , co-
solvents , complexation , micro emulsions , self-emulsifying
drug .

24. SOLUBILIZERS
– Dimethyl acetamide
– Ethanol
– Glycerol
– PEG 300
– Gelatin
– Pectin
– PEG 4000
CONCENTRATION
RANGE %
– 0.01
– 0.61 – 49.0
– 14.6 – 25.0
– 0.01 – 50.0
– 2.0
– 0.2
– 2.7 – 3.0

25. STABILIZERS
• As parenteral products are available in solution
from so they are more prone to unstabilize.
• Therefore, stabilizers are used to maintain the
stability of the product.
• The commonly used stabilizers are mentioned
below;

26. STABILIZERS
• Niacinamide
• Glycine
• Creatinine
• Sodium saccharin
• Sodium caprylate
CONCENTRATION %
• 1.25 – 2.5
• 1.5 – 2.25
• 0.5 – 0.8
• 0.03
• 0.4

27. ANTIMICROBIALAGENTS
• Aqueous preparations which are prepared using aseptic
precautions and which cannot be terminally sterilized may contain
a suitable anti microbial preservative in an appropriate
concentration.
• No antimicrobial preservative is added when:
 The volume to be injected in a single dose exceeds 15ml
unless otherwise justified.
 The preparation is intended for administration by routes where
for medical reasons are antimicrobial preservative is not
acceptable.
 If the drug formulation itself has sufficient anti microbial
activity.
• Antimicrobial agents are added to multiple dose vials to
inhibit the growth of micro organisms which may occur
accidentally and contaminate the product during use.

28. • The antimicrobial agents selected must be;
 Stable and effective in the parenteral formulation.
 Because they are effective in the free form , their activity can
be greatly reduced by interaction with components of the
injection.
 Rubber closures have been shown to take up antimicrobial
preservatives from the injection solution.
• The effectiveness of anti microbial agents can be tested by
challenging the product with selected organisms.
• The test procedure will evaluate the anti microbial activity of
the preservative in the packaged product ( refer BP 1998 ).

29. Table lists anti microbial agents commonly utilized in parenteral
formulations i.e. in sterile preparations
ANTI MICROBIALAGENTS
 Benzalkonium chloride
 Benzyl alcohol
 Chlorobutol
 Phenol
 Chlorocresol
 Phenylmercuric salts
 Methylhydroxybenzoate
 Thimerosal
 Propyl paraben
CONCENTRATION USED
( w/v % )
 0.01
 1 – 2
 0.25 – 0.5
 0.5
 0.1 – 0.3
 0.001
 0.1 – 0.2
 0.001 – 0.02
 0.05 – 0.035

30. ANTI TOXIDANTS
• Many drugs in aqueous solutions are easily degraded by
oxidation.
• Small volume parenteral containing these drugs often contain
an anti toxidants.
• Anti toxidants must be carefully selected for use in injections
to avoid interaction with the active.
• Anti toxidants have a lower oxidation potential than the active
and hence are either preferentially oxidized or block oxidative
chain reactions.
• The commonly known are given below;

31. ANTI TOXIDANTS
• Ascorbic acid
• Thiourea
• Sodium bisulphite
• Sodium metabisulphite
CONCENTRATION %
• 0.02 – 0.1
• 0.005
• 0.1 – 0.15
• 0.1 – 0.15